Early recognition of he’patode’lluIar ( ire inonia
- K. Okuda
- Hepatology Baltimore),
Reports of an increase in a serum epoxide hydrolase (sEH), immunochemically related to microsomal EH in humans and rats with hepatocellular carcinoma (HCC), suggested its use as a serum marker for this disease. We have now measured sEH levels (as either immunochemically determined content or enzyme activity) in a number of human and experimental models of liver disease. sEH was elevated above the normal range in at least 50% of individuals with HCC, including: 3 of 6 northern Californians; 4 of 7 Koreans with hepatitis B-associated HCC; hepatitis B-associated HCC in woodchucks; and male rats receiving chronic treatment with aflatoxin B1 or ciprofibrate. sEH was rarely elevated in other forms of chronic liver disease. Only 2 of 9 Koreans with hepatitis B-associated cirrhosis, 1 of 8 carriers, but none with chronic active hepatitis or infection with no apparent liver disease had elevated sEH. In addition, no elevations were found in woodchucks with noncancerous viral hepatitis. Received 9/18/90. 1 Supported in part by USPHS Grants ES02710, ES04699, (B. D. H.), CA27426 (B. H. R.), CA36130 )M. S. R.), CA40737, CA06927, RR05895 )W. T. LI. and CA24459 (M. I. G.(; by NIH Small Business Research Grant CA36660 (I. H. H.); I)y a grant from the University of California’s Cancer Research Coordinating Cumniittee ID. E. MI; and by a sniall grant from Kimberly Clark Corp. )M. I. G.). B. D. H. is a recipient of a BurroughsWellcome Toxicology Scholar Award. 2 To whom requests for reprints should be addressed, at present address: Center for Human Toxicology, University of Utah, 417 Wakara Way, Room 290, Salt Lake City, UT 84108. 3 Present address: Institute of Pharmacology, Syntex Research, Palo Alto, CA 94303. 4 Present address: Microbiology, Parasitology, and Pathology Department, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. S Present address: Department of Gastroenterology and Hepatology, Thomas lefferson University Hospital, Philadelphia, PA 19107. 6 Present address: G. D. Searle Research and Development, Searle & Co., Skokie, IL 60077. In aflatoxin B1and M1-treated rats sEH was not elevated in those with only hyperplastic foci or hepatocellular adenomas, and in two rat initiationpromotion protocols sEH was elevated only in those rats which received the entire set of treatments. sEH was also increased during acute hepatotoxicity in rats treated with Cd4 or 1,2-dibromo-3-chloropropane. The mechanism of increase in sEH during hepatocarcinogenesis appears to be different from that of other markers of HCC, for in the Korean patients, there was no correlation between sEH concentrations and those of a-fetoprotein or ferritin, nor was there a correlation with a-fetoprotein concentrations in the aflatoxin-treated rats. Furthermore, the increase in sEH does not correlate with induction of microsomal (H in the liver of experimental animals. Studies to date indicate that sEH is selective for HCC and severe hepatonecrotic injury, and may be of some use in the diagnosis of HCC, particularly as a complement to other serum markers.